14. Adrenergic receptors (adrenoceptors) - DOPAMIN Flashcards
Characteristics of adrenoceptors: α1 receptor
-> What is the main effect?
Constriction/Contraction
Characteristics of adrenoceptors: α1 receptor
-> Main effect: Constriction/Contraction
Blood vessels, bronchi, uterus, sphincters (GI, bladder),
iris (radial muscle)→midriasis
Liver hepatocytes: glycogenolysis
Examples of clinical use of adrenoceptors: α1 receptor
agonist:
hypotension
nasal congestion
used as a vasoconstrictor in local anesthetics to decrease their absorption
antagonist: hypertension; benign prostatic hypertrophy
Characteristics of adrenoceptors: α2 receptor
-> Main effects
presynaptic: feedback: inhibits NE release inhibits sympathetic (adrenergic) outflow
postsynaptic: vasoconstriction
pancreatic beta cells: decrease insulin secretion platelets: aggregation
Characteristics of adrenoceptors: α2 receptor
-> Example of clinical use (agonist)
hypertension treatment
(opiate) withdrawal treatment
vasomotor instability (‘hot flushes’)
Characteristics of adrenoceptors: α2 receptor
-> Example of clinical use (antagonist)
(not used clinically claimed to be aphrodisiac)
Glucose regulation of insulin secretion by ___- (which type of cells)
Pancreatic beta cell
Glucose regulation of insulin secretion by pancreatic beta cells
1/ Glucose transporter GLUT2
2/ ATP-gated K+ channel
3/ Voltage-gated Ca2+ channel
Where are Incretins (Glucagon-like peptide 1 [GLP-1]) released?
They are released from neuroendocrine cells of the gastrointestinal tract
Incretins (Glucagon-like peptide 1 [GLP-1])
are released from neuroendocrine cells of the gastrointestinal tract following food ingestion and amplify ___ and ___
glucose-stimulated insulin secretion and suppress glucagon secretion.
What are GLP-1 agonists?
pharmacologic agents that prolong the activity of endogenous GLP-1 enhance insulin secretion.
What does this slide indicate?
Structure of the β-adrenergic receptor in the active states and its associated trimeric G protein
What does this slide indicate?
Structure of the β-adrenergic receptor in the active states and its associated trimeric G protein
Characteristics of adrenoceptors: β1 receptor
-> What are the main effects of adrenoceptors: β1 receptor?
increase heart rate, force of contraction renin release
lipolysis
Characteristics of adrenoceptors: β1 receptor
-> What are the examples of clinical use (agonist)?
severe cardiac failure
Characteristics of adrenoceptors: β1 receptor
-> What are the examples of clinical use (antagonist)?
antagonist (beta blockers):
prevent heart ischemia
hypertension social fobia
Characteristics of adrenoceptors: β1 receptor
-> Identify 1
ACE inhibitors
Characteristics of adrenoceptors: β1 receptor
-> What can inhibit AT1 receptors?
Angiotensin II
AT1 subtype receptor antagonists
Characteristics of adrenoceptors: β2 receptor
-> What is the main effect?
Main effect: dilate/relax
blood vessels, bronchi, uterus, GI, sphincter (bladder), ciliary muscle→miosis
Liver, muscle: glycogenolysis
Mast cells: inhibition of histamine release
Characteristics of adrenoceptors: β2 receptor
-> What is an example of clinical use - agonist?
bronchodilators (asthma)
(also inhibit mediator release from mast cells)
Characteristics of adrenoceptors: β2 receptor
-> Identify
cAMP-dependent protein kinase
Characteristics of adrenoceptors: β2 receptor
-> What is happening at 1 & 2?
1/ Myosin light chain kinase is active
2/ Myosin light chain is phosphorylated
Characteristics of adrenoceptors: β2 receptor
-> What is happening here?
reduced sensitivity of MLCK to the Ca2+ -calmodulin complex
Characteristics of adrenoceptors: β2 receptor
-> What will happen at 1 & 2?
1/ contraction
2/ smooth muscle relaxation
Characteristics of adrenoceptors: β3 receptor
-> What is the main effect?
relax bladder
lipolysis
thermogenesis
Examples of clinical use of adrenoceptors: β3 receptor
agonist:
overactive bladder
Identify
Characteristics of VMAT 2 - vesicular monoamine transporter 2?
Broad substrate-specificity to biogenic amines
(tryptamine, tyramine, amphetamine – compete with endogenous catecholamine)
Identify 1 & 2
1/ Dihydroxyphenylacetic acid (DOPAC)
2/ Homovanilic acid (HVA)
List Dopaminergic receptors types
Dopaminergic receptors
-> The role of D1 type
Dopaminergic receptors
-> The role of D2 type
Examples of endogenous Neurotoxins
metabolites of catabolism:
DOPAL
Exogenous neurotoxins
-> The mechanism of MPTP
(1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine)
Taken up by dopaminergic nerve terminals – metabolized by MAO-B
-> 1-methyl-4-phenyl-pyridinium (MPP+) - active toxic metabolite – complex I inhibitor
Exogenous neurotoxins
-> Where do MPTP present?
In the i.v. narcotic drug heroin as a contaminant
The role of Cycad tree
tropical seed contains ß-methyl-amino- L-alanin (BMAA) produced by cyanobacteria found in the roots of cycads
does Dopamine cross the blood-brain barrier?
Dopamine does not cross the blood-brain barrier (BBB)
does Dopamine cross the blood-brain barrier?
Dopamine does not cross the blood-brain barrier (BBB)
Drugs in therapy of Parkinson’s disease
-> name of these inhibitors
Drugs in therapy of Parkinson’s disease
-> name of these inhibitors
Drugs in therapy of Parkinson’s disease
-> Identify
Dopamine agonists act directly on dopamine receptors
Dopaminergic reward system
-> What are the rewards?
Rewards: mediate the effects of reinforcement
Dopaminergic reward system
-> What are the primary rewards?
necessary for survival (food, water, sexual contact, physical contact (cuddling), successful agression)
Drugs interfere with Dopaminergic reward system
-> How?
Produce some of the effects of natural rewards (but not others, such as emotional effects, memory etc)
